Comparison of Negative Inotropic and Vasodilator Effects of Isradipine and Nifedipine After Complete Autonomic Blockade in Ischemic Heart Disease

Summary: The cardiodepressant and vasodilator effects of an intravenous (i.v.) infusion of 0.5 mg isradipine or 2 mg nifedipine were interindividually (10 vs. 10 patients) compared in a double-blind study in patients with stable coronary heart disease. To minimize vasodilation-induced autonomic reflex mechanisms, which may counterbalance negative inotropic effects after acute administration of calcium antagonists, i.v. autonomic blockade was produced by 0.2 mg/kg propranolol and 0.04 mg/kg atropine. Systemic hemodynamics were measured before and 15 min after the end of the 15-min calcium antagonist infusion. After administration of both drugs, heart rate (HR) decreased similarly during the observation period (isradipine from 93 ± 10 to 88 ± 9 beats/min and nifedipine from 84 ± 9 to 79 ± 6 beats/min, both p ≤ 0.01). The reduction in total peripheral resistance (TPR) was significantly (p ≤ 0.01) greater after isradipine (from 1,376 ± 285 to 1,002 ± 224 dynes s cm “ s) than after nifedipine (1,258 ± 262 to 1,112 ± 225 dynes s cm-5). Between the two drugs, the difference in the reduction of afterload independent dP/dt40, determined by tip-manometry, reached borderline significance (p = 0.08) (isradipine from 1,197 ± 258 to 1,157 ± 225 mm Hg/s, NS and nifedipine 1,228 ± 226 to 1,109 ± 227 mm Hg/s, p =s 0.01). There was a significant difference (p =s 0.05) in the behavior of left ventricular end-diastolic pressure (LVEDP), which increased after nifedipine from 8 ± 5 to 11 ± 4 mm Hg (p =s 0.01) and decreased insignificantly after isradipine from 14 ± 10 to 12 ± 7 mm Hg. These data suggest that isradipine separates, more than nifedipine, vasodilating from negative inotropic effects, and that isradipine has more vasodilator and fewer cardiodepressant effects than nifedipine.